The fault of autoantibodies ? Explaining the rare cases of thrombosis linked to the AstraZeneca vaccine

Thromboembolic events are a rare but serious side-effect of the AstraZeneca adenovirus vaccine. A clot forms, blocking a vein or an artery, and can cause a pulmonary embolism. Thromboembolic disease exists naturally (that is, not linked to the AstraZeneca vaccine) in the general population, with some 130 000 hospitalisations in France in 2014. Some risk factors exist, such as cancer, obesity, pregnancy or the contraceptive pill.

Canadian researchers (at McMaster University and the McMaster Centre for Transfusion Research, Hamilton) studied 5 patients, 2 women and 3 men, from 35 to 72 years old (with an average age of 44), who had suffered a thromboembolic event after their 1^st AstraZeneca vaccine. They were able to confirm the presence of autoantibodies, that is, rogue antibodies that identify a target and bind themselves to it. In this case, autoantibodies attacked the platelet factor 4 (PF4), which is an integral part of the self, in all these patients. The scientists therefore confirmed the responsibility of these antibodies in these cases of vascular accident.

This illness is caused by the appearance of autoantibodies which, in binding to the PF4, form an immune complex. This complex leads to the activation of platelets and, potentially, of other cells too. This provokes coagulation at multiple sites, causing the formation of clots and consequently thrombosis and thrombocytopenia (a reduction in the number of platelets in the blood). The scientists mapped the epitopes (antibody binding sites) on the PF4 and thus identified 8 amino acids on the surface of the protein with which the antibodies bind.

This study has allowed the role of autoantibodies targeting the PF4 platelet factor in thromboembolic events after vaccination with AstraZeneca to be confirmed. It remains possible that this mechanism is not solely responsible for the strokes that result.